1. Intercalated chemotherapy and erlotinib for advanced NSCLC : high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutationsMatjaž Zwitter, Karmen Stanič, Mirjana Rajer, Izidor Kern, Martina Vrankar, Natalija Edelbaher, Viljem Kovač, 2014, izvirni znanstveni članek Povzetek: Background. Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC). Patients and methods. Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance. Results. Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2%3 (11 patients - 21%) and brain metastases (15 patients - 28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months. Conclusions. While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.
Ključne besede: non-small cell lung cancer, EGFR activating mutations, gemicitabine, erlotinib
Objavljeno v DiRROS: 11.04.2024; Ogledov: 82; Prenosov: 20
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2. Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer : a randomized phase II clinical trialMartina Vrankar, Matjaž Zwitter, Tanja Bavčar-Vodovnik, Ana Milič, Viljem Kovač, 2014, izvirni znanstveni članek Povzetek: The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results. From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions. Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance
Ključne besede: induction chemotherapy, non-small cell lung cancer, radiation therapy, randomized clinical trial
Objavljeno v DiRROS: 11.04.2024; Ogledov: 81; Prenosov: 20
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3. Priporočila za obravnavo bolnikov s pljučnim rakomMartina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Marina Čakš, Dominik Časar, Eva Ćirić, Tanja Čufer, Ana Demšar, Rok Devjak, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Marija Ivanović, Urška Janžič, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Loredana Mrak, Igor Požek, Nina Turnšek, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2023, strokovni članek Povzetek: Leta 2019 so bila objavljena Priporočila za obravnavo bolnikov s pljučnim rakom, ki so v slovenski prostor vnesla prepotrebno poenotenje diagnostike in zdravljenja z namenom izboljšanja preživetja bolnikov s pljučnim rakom. Posodobitev Priporočil tri leta po izidu izvirnika prinaša največ novosti v poglavju o sistemskem zdravljenju bolnikov s pljučnim rakom. To kaže na izjemen napredek na področju razumevanja onkogeneze in biologije pljučnega raka ter s tem razvoja novih zdravil. Breme pljučnega raka ostaja veliko, saj je pljučni rak pri nas in v svetu še vedno najpogostejši vzrok smrti zaradi raka. Za vsako peto smrt zaradi raka je odgovoren pljučni rak. Skoraj tretjina bolnikov s pljučnim rakom ne prejme specifičnega onkološkega zdravljenja, bodisi zaradi slabega stanja zmogljivosti, spremljajočih bolezni ali obsega bolezni. Polovica bolnikov ima ob diagnozi razsejano bolezen, zaradi česar izboljšanje preživetja z malimi koraki sledi napredku v zdravljenju bolnikov s pljučnim rakom. Ti podatki nas opominjajo, da se bomo morali za velike premike v obravnavi bolnikov s pljučnim rakom lotiti drugačnih pristopov. Kot najbolj obetavno se ponuja zgodnje odkrivanje bolezni, ko so možnosti ozdravitve pljučnega raka najboljše. Zapisana Priporočila so usmeritev za obravnavo bolnikov s pljučnim rakom. Le s sodobnim multidisciplinarnim pristopom obravnave lahko bolniku ponudimo zdravljenje, ki mu omogoča najboljši izhod prognostično neugodne bolezni.
Ključne besede: pljučni rak, priporočila
Objavljeno v DiRROS: 27.07.2023; Ogledov: 379; Prenosov: 136
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4. Fizikalni modeli imunoterapije in radioterapijeDamijan Valentinuzzi, Martina Vrankar, Katja Uršič Valentinuzzi, Mojca Unk, Olga Gordeeva, Alen Hadžić, Gregor Serša, Maja Čemažar, Robert Jeraj, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: V prispevku bomo predstavili rezultate fizikalnih modelov imunoterapije, ki smo jih razvili v programski skupini Medicinska fizika na Fakulteti za matematiko in fiziko Univerze v Ljubljani. Glavni cilj raziskav je bila prepoznava bioloških značilnosti tumorjev, od katerih je odvisen odziv na zdravljenje s protitelesi receptorja programirane celične smrti l (angl. anti-programmed-death-1 (anti-PD-1)). Posebno pozornost smo namenili meritvam modelskih parametrov ter preverbi rezultatov modeliranja, kar je eden izmed predpogojev za uspešno translacijo modeliranja v rutinsko predklinično in klinično prakso. Predstavili bomo tudi načrte za prihodnost, tj. modeliranje kombinacije anti-PD-1 in radioterapije.
Ključne besede: imunoterapija, radioterapija, medicinska fizika, tumorji
Objavljeno v DiRROS: 16.06.2023; Ogledov: 365; Prenosov: 96
Celotno besedilo (2,01 MB) |
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6. Pljučni rak - nacionalni problemMartina Vrankar, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Breme pljučnega raka v Sloveniji v zadnjem desetletju ostaja nacionalni problem. Incidenčna
stopnja se je pri moških sicer ustalila v zadnjih nekaj desetletjih, podatki pri ženskah pa
kažejo na strm porast incidence v zadnjem desetletju, saj vsako leto zboli za skoraj 6 % več
žensk. Kar dobra polovica bolnikov s pljučnim rakom ima ob diagnozi razsejan pljučni rak, ki
ga kljub sodobnim načinom zdravljenja ne moremo pozdraviti. Po umrljivosti je pljučni rak
pri moških in pri ženskah na prvem mestu. Vsako peto smrt zaradi raka pripišemo pljučnemu
raku. Petletno preživetje bolnikov, zbolelih v obdobju 2015–2019, je bilo 19,5 %, bolnic pa
26,4 %. Izzivi v prihodnosti so v zgodnejšem odrivanju pljučnega raka. Raziskave so pokazale,
da lahko presejanje pljučnega raka zniža umrljivost za 20 %, saj omogoča odkrivanje zgodnjih
oblik raka. V presejalni program pljučnega raka morajo biti vključeni učinkoviti programi za
opuščanje kajenja, prav tako pa je potrebno intenzivirati aktivnosti primarne preventive.
Ključne besede: pljučni rak, onkološko zdravljenje, bolniki
Objavljeno v DiRROS: 12.05.2023; Ogledov: 254; Prenosov: 151
Celotno besedilo (149,13 KB) |
7. Priporočila za obravnavo bolnikov s pljučnim rakomMartina Vrankar, Nina Boc, Izidor Kern, Aleš Rozman, Karmen Stanič, Tomaž Štupnik, Mojca Unk, Maja Ebert Moltara, Vesna Zadnik, Katja Adamič, Jernej Benedik, Marko Bitenc, Jasna But-Hadžić, Anton Crnjac, Eva Ćirić, Tanja Čufer, Goran Gačevski, Marta Globočnik Kukovica, Kristina Gornik-Kramberger, Maja Ivanetič Pantar, Staša Jelerčič, Veronika Kloboves-Prevodnik, Mile Kovačević, Luka Ležaič, Mateja Marc-Malovrh, Katja Mohorčič, Bogdan Vidmar, Dušanka Vidovič, Gregor Vlačić, Ana Lina Vodušek, Rok Zbačnik, Ivana Žagar, 2022, ni določena Ključne besede: elektronske knjige
Objavljeno v DiRROS: 24.11.2022; Ogledov: 658; Prenosov: 212
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10. PD-L1 expression can be regarded as prognostic factor for survival of non-small cell lung cancer patients after chemoradiotherapyMartina Vrankar, Matjaž Zwitter, Izidor Kern, Karmen Stanič, 2018, izvirni znanstveni članek Povzetek: The standard treatment for inoperable locally advanced non-small cell lung cancer (LA NSCLC) includes concurrent or sequential chemotherapy (ChT) and radiation therapy (RT). Long term survival rates with these approaches remains only in the order of 15%, therefore new treatment strategies, including immunotherapy, are under investigation, with programmed death ligand-1 (PD-L1) as one of the major players. We evaluated the clinical significance of PD-L1 expression in tumor samples from patients with inoperable LA NSCLC who underwent concurrent chemoradiotherapy (CRT) in our institution between 2005 and 2010 and correlated their expression with clinicopathological parameters and outcome of treatment. Among 107 patients treated with concurrent CRT, a total of 43 (36 males and 7 females) had sufficient tissue for immunohistochemical (IHC) staining. The expression of PD-L1 was demonstrated in 7 tumors, in 6 males and 1 female. No statistical significant differences in patient characteristics, including age, smoking status and gender, were found according to the PD-L1 expression. After a median follow up of 103.6 months, median progression free survival (PFS) was 19.9 months in patients without and 10.1 months in patients with PD-L1 expression (p=0.008). Median overall survival (OS) was 28.4 and 12.1 months for PD-L1 negative and PD-L1 positive patients, respectively (p=0.012). In conclusions, patients with PD-L1 expression had shorter PFS and OS after concurrent CRT in LA NSCLC. Unfortunately, only small number of patients had tissue available for the IHC testing, therefore no firm conclusions could be made and further investigation is warranted.
Ključne besede: non-small cell lung cancer, lung cancer, chemoradiotherapy, survival
Objavljeno v DiRROS: 17.12.2020; Ogledov: 1323; Prenosov: 417
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